1. Field of Invention
This invention relates to mixtures of sugars useful for reducing caloric intake and glycemic index.
2. Prior Art
Americans' rapidly increasing consumption of added sugars over the last fifteen years has contributed significantly to a major public health problem, the reversal of which the US Center for Disease Control and Prevention (Koplan and Fleming, J Am Med Assn, 284, 1696, 2000) has targeted as one of its ‘top ten’ health goals for the 21st century. The problem is the epidemic of obesity in the US. Obesity is defined as a body weight 30% above the ideal body weight. Obesity is strongly linked with greater risk of heart disease, high cholesterol and blood pressure, type 2 diabetes, stroke and breast, colon and prostate cancers. A recent study has shown that more than 50% of Americans are overweight, and 22% are obese.
Over the 8-year period from 1991 to 1999, obesity among American adults rose from 12.0% to 18.9%, an increase of 57%. Coincident with the rise in obesity came a 33% increase in type 2 diabetes (from 4.9% to 6.5% overall). In a Reuters news article, dated Jan. 26, 2001, Dr. Ali Mokdad of the CDC's National Center for Chronic Disease Prevention and Health Promotion was quoted as saying, “We've seen a tremendous increase in obesity in the 90's—that's why we're now seeing an increase in diabetes.” He went on to say, “Obesity is no longer a cosmetic issue, but a risk factor for serious illness. We need to change our behaviors to reduce many of the chronic diseases we are facing, not only diabetes.”
The average American now consumes more than 80 grams of added sugars (typically as sucrose, glucose and fructose) each day. Added sugars are those sugars that are incorporated by man into processed foods and beverages, and do not include sugars that are naturally present in the natural and processed foods that we eat. Over the 8-year period from 1991 to 1999, adult consumption of added sugars rose from 70 to 80 grams/day while consumption of fat (and presumably protein) remained fairly constant. The average adult body weight over the same time period increased 2.9 lb, from 166.5 lb to 169.4 lb. We assume a constant level of activity for the adult over the 8-year period. Then, the increased consumption of added sugars (10 grams/day×3.9 kcal/gram=39 kcal/day vs an average 2000-kcal/day diet) alone can account for 3.2 lb, or all of the body weight increase observed over the 8-year span. Clearly, added sugars are important in controlling unwanted weight gain in adults.
The US Department of Agriculture recommends that an adult who eats a 2000-kcal/day healthful diet should try to limit himself or herself to consumption of about 40 grams of added sugars per day, or 8% of total caloric intake. This level of consumption is ½ of the current level of added sugars, with ½ of the associated calories. The subject invention allows one to continue consuming 80 grams of added sugars per day, but with no more than the caloric intake of the USDA-recommended 40 grams per day of added sugars. The subject invention, in addition, allows one to consume the same sugars that have gained acceptability (e.g. safety, quality of taste, ease of use in foods, and low cost) for many decades without exposure to any new or rare carbohydrates, carbohydrate derivatives, rare plant extracts, or artificial sweeteners.
Fructose, lactose and sucrose are widely consumed natural sugars in the American human diet (37, 16 and 81 grams/capita/day, respectively). All are known to be fully caloric (i.e., approximately 4 kcal/gram) when used separately in typical foods. It is known that ingestion of any of the three cited sugars as part of diet does not interfere with absorption of glucose, protein, or lipid from the small intestine. In fact, no report of any interaction of fructose, lactose, or sucrose with other human dietary components to reduce caloric utilization or raise glucose tolerance in animals or man has been reported previously. It is widely known (Wolever, 1995) that fructose has a substantially lower glycemic index (23) than lactose (46), sucrose (61 to 64), glucose (100), or oat starch (100). Because of their low glycemic indexes, fructose and lactose separately have been posed as useful for diabetics (Wolever et al, 1985 and Wolever et al, 1995), but no synergy between the two sugars or with other sugars has previously been disclosed that would suggest lower-than-expected glycemic indices or reduced caloric utilizations.
With the aforementioned facts about the three subject sugars in mind, the literature reveals prior art in the field of carbohydrate utilization. Eleven animal studies conducted over the past eight decades have shown inconsistent results, which bear on the apparent caloric value of lactose. The results from rats and pigs, the only two animals reported, were not always consistent with human results.
For example, Whittier et al (1935), Tomarelli et al (1960), and Baker et al (1967) studied the effect of lactose (30%, 52%, and 50% of diet, respectively) with glucose in pair-fed and ad libitum diet as the only two sources of carbohydrate in growing rats' diet, as compared to sucrose or glucose in control diet. All three research groups found lower body weight and body fat in the ad libitum-lactose-fed, sacrificed rats. Pair-fed rats showed the same body weight but lower body fat for lactose vs controls (down 38%, 40%, and 48% respectively). Whittier et al confirmed the lower fat weight effect in pigs fed restricted diets including lactose and brewers' yeast and even found increased longevity in rats fed lactose. Tomarelli et al attributed the observed fat-sparing effect of lactose largely to bacterial action of the disaccharide in the cecum. Similar reduced body fat weights were observed in rats fed sorbitol, cellobiose, and raw potato starch (resistant starch), all of which are poorly absorbed carbohydrates that undergo bacterial degradation in the cecum. The authors noted in exploratory experiments the blood glucose levels of rats fed glucose and lactose diets were not significantly different. Baker et al found a greater hypolipogenic effect with the β-anomer of lactose than with the α-anomer.
Février (1969) studied the effect of lactose (30% of diet) with corn starch (32.7% of diet) as the only sources of carbohydrate in ad libitum, pair-fed, and equal-growth diets in growing rats, as compared to a starch (62.7%) control. Ad libitum feeding resulted in a 37% reduction of growth rate and 20% reduction of fat content for the lactose-fed rats. Pair-feeding resulted in a 23% reduction of growth rate and 32% reduction of fat content for the lactose-fed rats. Equalized-growth-feeding resulted in a 12% reduction of fat content for the lactose-fed rats. The author asserted that the cause of the body fat reduction was the lower metabolizable energy of the lactose and a loss of galactose in the urine.
Dalderup et al (1969) reported that adult male rats fed 15 calorie % lactose in potato and bread starch diet over four months excreted a significantly larger amount of feces and formed a larger amount of lactic acid in feces compared with a 15-calorie % glucose group. These two observations support the notion that lactose in rats is not well-absorbed in the small intestine and is fermented in the cecum and/or colon.
Ali and Evans (1971) studied the growth of weanling male rats fed ad libitum “equicaloric” diets containing either 0 or 12% lactose over a six-week period. The basal diet included 30% starch and 30% sucrose. Lactose was added to the basal diet at the expense of part of the sucrose. The work was directed to study effects and interactions of dietary lactose and other dietary components on gross body composition in the growing rat, by multi-variable regression analysis. Lactose did not have any effect on diet consumption or body protein vs basal diet. The most pronounced effects were those of lactose on body fat (reduced 30%) and on body moisture (increased 11%). Although interactions between lactose and other dietary components (such as calcium, buffering capacity, and EDTA) were noted, the authors did not identify any interactions between lactose and either starch or sucrose.
Two rat and pig studies tangential to the subject of lactose utilization in diets containing starch found other interesting effects of lactose consumption. In growing pigs and rats, Cheeke et al (1973) found that lactose reduced the digestibility of alfalfa fiber and purified cellulose in the cecum and gut. The effect was admittedly counter-intuitive, and the authors offered no rational explanation. Conclusions were based on weight gains only; no determinations of body moisture, minerals, or fat were made. In another publication, Moser et al (1980) studied postweanling rats fed graded diets in which 30% starch was replaced with increasing amounts of lactose up to 30%. A trend toward poorer growth rate was noted as lactose increased in the diet. Rats fed 30% lactose had the poorest feed efficiency of all groups. Body fat was not measured, but ash was determined in femurs. Percentage ash increased linearly as lactose increased.
Jin et al (AJAS, 11 (3), 285, 1998) found that weaned pigs fed diets containing lactose (20%) and corn (36.5%) vs sucrose (20%) and corn (36.5%) were completely equivalent after 3 weeks of feeding. Average daily gain and average daily feed intake were the same for both groups. Complete body composition analysis was not performed, but clearly there was no sign of an interaction of the starch from corn with lactose or with sucrose.
Jin et al (AJAS, 11 (2), 185, 1998) reported the results of a study to optimize the ratio of lactose to sucrose for weaned pigs fed ad libitum diets containing graded fractions of lactose (20%) at the expense of sucrose (20%) for three weeks: Both diets contained corn (38.5%) as a source of starch. For the third week, there were no differences among the groups with respect to average daily gain (G), average daily feed intake (F), and the ratio F/G. At the end of three weeks, digestibility of nutrients—dry matter, crude fat, and phosphorus—were not influenced by the varying lactose: sucrose ratio. On the other hand, pigs fed lactose at 10%, 15%, or 20% showed significantly improved nitrogen digestibility. The authors propose that the improvement in nitrogen digestibility may be due to the high level of lactase enzyme present in the small intestine of the young pig. Clearly the pig handles digestion of lactose more efficiently than the rat. The difference between the pig and rat model raises the question of which one has more relevance to man.
In an article published in 1979 by Karimzadegan et al, the relative availability of lactose in rats compared to glucose was determined in bioassays based on weight gain and plasma ketones to be 0.57 and 0.59, which values correspond to a metabolizable energy value for lactose of 2.1 kcal/g. The energy value widely accepted in man and reported in a leading lactose-manufacturer's data sheet (Foremost, 1995) is 3.8 kcal/g. The lower energy value for lactose in rats is due to the much lower activity of the lactase enzyme in the small intestine of the postweanling and adult rat. Because the dietary lactose cannot be hydrolyzed completely in the small intestine, it passes into the cecum and colon where bacteria degrade it less energy-efficiently to lactic acid, to short chain fatty acids (SCFA's), and to carbon dioxide and hydrogen. In retrospect, it is the low caloric value of lactose that largely accounts for the observed hypolipogenic effect, the lower growth rate, and the poor feed efficiency in rats. A historically unrecognized interaction between lactose and starch may account for part of these effects also.
A number of interferences between sucrose-absorption in vivo and small carbohydrate molecules are known or can be surmised. Sugimoto (1976) claimed the use of maltitol and lactitol for reducing cholesterol levels resulting from sucrose consumption. The claimants elaborated that these two carbohydrate derivatives inhibit the “absorbance” of sucrose in vivo. Similarly, Seri et al (1995) claimed the use of a number of pentoses, 2-deoxy-D-galactose, and D-tagatose as antihyperglycemic remedies, which work by inhibiting sucrase and maltase, the enzymes responsible for hydrolysis of sucrose and maltose, respectively, prior to absorption of the disaccharides in the small intestine. Although Gray and Ingelfinger (1966) reported inhibition of sucrose hydrolysis in man by galactose, Seri et al (1995) saw no inhibition of rabbit sucrase or maltase by galactose in vitro, and Alpers and Gerber (1971) saw no inhibition of human intestinal sucrase either. Gray and Ingelfinger (1966) concede that the galactose inhibition they observed is likely due to interference with the active absorption of glucose by galactose, since both monosaccharides use the same active transport mechanism. Fructose and glucose have been reported to inhibit the hydrolysis of sucrose by human sucrase in vitro (Alpers and Gerber, 1971). No interactions between lactose and sucrose-absorption have been reported previously, to our knowledge.
Other than the Seri et al (1995) claims, only one interference of a small carbohydrate molecule with maltose-absorption in vivo is known to the claimants. Maltose is the predominant disaccharide that forms by α-amylase-catalyzed hydrolysis of starch. The sole product of maltose hydrolysis, glucose, also inhibits the maltase-catalyzed hydrolysis of maltose in vitro (Alpers and Gerber, 1971). Fructose and galactose have no inhibiting effect on maltose hydrolysis in vitro (Alpers and Gerber, 1971). No interactions between lactose and maltose-absorption have been reported previously, to our knowledge.
Several interferences between lactose-absorption and small carbohydrate molecules in vivo may be suggested in the literature but are not obviously applicable to everyday dietary understanding. Glucose, galactose, and fructose have been reported to competitively inhibit hydrolysis of lactose by human lactase in vitro (Alpers and Gerber, 1971). Sucrose and maltose have no inhibiting effect on lactose hydrolysis in vitro (Alpers and Gerber, 1971). Based on the abovementioned in vitro interferences alone, it would not be obvious to one skilled in the art that lactose absorption in human small intestine would be strongly inhibited (enough for lactose to interfere with sucrose and maltose absorption) by glucose, galactose, and fructose, all of which are absorbed rapidly (glucose and galactose are absorbed approximately 1.7 and 1.2 times as fast as fructose) in the human small intestine (Gray and Ingelfinger, 1966).
Wolever et al (1985) compared the effect of added lactose (25 g) with added sucrose (25 g), fructose (25 g), and glucose (25 g) to porridge oats (21.5 g) on the acute blood glucose responses of six diabetic volunteers, directly after their normal use of insulin or oral diabetes agents. The calculated glycemic indices (GI's) for the respective sugars vs glucose (GI=100) were 48, 63, 24, and 90; all, except glucose, agree well with GI's reported for normal subjects. The subjects considered the sucrose and fructose sweeter than lactose and glucose, but tended to prefer the taste of the less sweet meals. No symptoms suggestive of lactose malabsorption were observed. The authors suggested that the long-term effects of lactose on blood lipids need further study. No interaction of added lactose, or of any other added sugar, with starch was reported.
Gannon et al (1986) compared untreated diabetics' plasma glucose and serum insulin responses for sucrose, glucose, fructose, glucose+fructose, or lactose in portions that contained 50 g of total carbohydrate, both in natural foods, like fruits and milk products, and as pure substances. The glucose responses were essentially the same whether the carbohydrates were given in pure form or in naturally occurring food. In general, the blood glucose areas under the curve (AUC) could be predicted by the known metabolism of the constituent monosaccharides. Insulin responses, however, were not always predictable, particularly in the case of milk, which contains a powerful insulin secretagogue.
Food articles tested by Gannon et al included ice cream, which contained 34 g sucrose and 16 g lactose (along with 7.4 g protein and 13.2 g fat). In summary, the authors stated, “ . . . the single meal plasma glucose response is characteristic for each type of mono- or disaccharide in a food, and is little influenced by other constituents present in these meals.” The claimants disagree strongly with this generalization and feel that Gannon et al missed the interaction of lactose and sucrose to reduce plasma blood glucose in ice cream perhaps because the diabetic subjects were not allowed to take insulin or diabetes drugs prior to testing; consequently, the 50-g carbohydrate dose was too large for the AUC to respond in a linear manner to changes in glucose absorption. The GI's that Gannon et al found were not consistent with those from Wolever et al (1985). For example, Gannon et al found GI values for sucrose, fructose, and lactose of 43, 6, and 32, compared with 63, 24, and 48 from Wolever. The latter Wolever values are well-known and widely accepted by other researchers.